Cathelicidins and functional analogues as antisepsis molecules

Neeloffer Mookherjee, Linda M. Rehaume, Robert E.W. Hancock

Research output: Contribution to journalReview articlepeer-review

90 Citations (Scopus)

Abstract

The emergence of antibiotic-resistant bacteria together with the limited success of sepsis therapeutics has lead to an urgent need for the development of alternative strategies for the treatment of systemic inflammatory response syndrome and related disorders. Immunomodulatory compounds that do not target the pathogen directly (therefore limiting the development of pathogen resistance), and target multiple inflammatory mediators, are attractive candidates as novel therapeutics. Cationic host defence peptides such as cathelicidins have been demonstrated to be selectively immunomodulatory in that they can confer anti-infective immunity and modulate the inflammatory cascade through multiple points of intervention. The human cathelicidin LL-37, for example, has modest direct antimicrobial activity under physiological conditions, but has been demonstrated to have potent antiendotoxin activity in animal models, as well as the ability to resolve certain bacterial infections. A novel synthetic immunomodulatory peptide, IDR-1, built on this same theme has no direct antimicrobial activity, but is effective in restricting many types of infection, while limiting pro-inflammatory responses. The ability of these peptides to selectively suppress harmful pro-inflammatory responses, while maintaining beneficial infection-fighting components of host innate defences makes them a good model for antisepsis therapies that merit further investigation.

Original languageEnglish
Pages (from-to)993-1004
Number of pages12
JournalExpert Opinion on Therapeutic Targets
Volume11
Issue number8
DOIs
Publication statusPublished or Issued - 2007
Externally publishedYes

Keywords

  • Cathelicidin
  • Host defence peptide
  • Inflammation
  • Pattern recognition receptor
  • Sepsis

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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